Fish Consumption, Omega-3 Fatty Acids, and Cardiovascular Disease
By Rakesh Calton, MD
Associate Professor, Clinical Foundations, Ross University School of Medicine, Barbados, West Indies
SYNOPSIS: Is there enough scientific evidence to suggest associations between fish consumption and risk of cardiovascular disease (or of mortality) among people who consume fish vs. those who do not?
SOURCE: Mohan D, Mente A, Dehghan M, et al. Associations of fish consumption with risk of cardiovascular disease and mortality among individuals with or without vascular disease from 58 countries. JAMA Intern Med 2021;181:631-649.
Eating a lot of fish, a rich source of long-chain omega-3 fatty acids, has been shown to improve cardiovascular disease (CVD) risk.1-3 Various studies have shown a beneficial role of omega-3 fatty acids in managing CVD, hyperlipidemias, and hypertension.1-3 However, the literature does not provide conclusive evidence.4 While some researchers have found a positive correlation in omega-3 fatty acid consumption and improvement in CV events, coronary heart diseases, and CV event-related mortality, other authors did not show similar beneficial effects. Mohan et al hypothesized that since eating more fish improves blood lipid levels, there should be significant differences in the association between fish intake and CV outcomes and mortality among those with CVD vs. those without.
Mohan et al conducted a pooled analysis between January 2020 and June 2020 of participant data obtained from 191,558 individuals from four cohort studies. The data taken from Prospective Urban Rural Epidemiology (PURE) in 21 countries included 147,645 individuals (mean age 54.1 ± 8 years), 139,827 of whom did not have CVD, while 7,818 had preexisting CVD. All outcome events known until July 31, 2019, were included in the analysis. The other data were obtained from 43,413 participants published in three prospective studies from 40 countries: The Ongoing Telmisartan Alone and in Combination with Ramipril Global End Point Trial (ONTARGET), a randomized, clinical trial of antihypertensive medication for 25,620 patients age 55 years or older; data from 5,926 participants of the Telmisartan Randomized Assessment Study in ACE-Intolerant Subjects with Cardiovascular Disease (TRANSCEND), a randomized, controlled trial of telmisartan vs. placebo; and data from 12,422 participants from the Outcome Reduction with Initial Glargine Intervention (ORIGIN) trial.
Variables collected from all studies included demographic factors, lifestyle, health history, and medication. Physical assessment included data on weight, height, waist, hip circumference, and blood pressure. In the PURE study, habitual food intake was recorded using country-specific validated food frequency questionnaires (FFQ). In ONTARGET and TRANSCEND, dietary information was obtained using a 19-question FFQ. The ORIGIN study authors used a 25-question, qualitative FFQ on individual foods. However, for fish consumption, they used a separate 28-question FFQ. Statistical analysis involved a calculation of adjusted hazard ratio (HR) by multilevel Cox regression analysis within each of the studies and then pooling using a random-effects meta-analysis.
Median fish intake was calculated overall, as well as for the geographical regions, with adjustments made for age and gender. For each cohort, participants were divided into groups based on their fish consumption: less than 50 g per month, between 50 g and 175 g per month, between 175 g and 350 g per month, and more than 350 g per month. An analysis of covariance was performed to determine mean lipid blood levels and blood pressure levels among fish intake groups, adjusted for covariates. A two-stage participant meta-analysis also was performed. In the first stage, association between fish intake and events in each cohort were determined separately. In the second stage cohort, specific HRs and 95% confidence intervals (CIs) were pooled in a random-effects meta-analysis. Proportionality assumption was tested using a global goodness-of-fit test and Schoenfeld residuals in each cohort. A test of heterogenicity was conducted by employing the I2 statistic. Additionally, for the PURE study, Cox frailty models with random effects were used to correlate between fish intake and the outcomes.
A total of 191,558 participants with a mean age of 54.1 ± 8.0 years were included in the analysis. Of these, 91,666 were men. In PURE, over a follow-up of 9.1 years, intake of 350 g/week or more was not associated with risk of major CVD (HR, 0.95; 95% CI, 0.86-1.04) or total mortality (HR, 0.96; 95% CI, 0.88-1.05).
In the other three cohorts, the HR for risk of major CVD (HR, 0.84; 95% CI, 0.73-0.96) and total mortality (HR, 0.82; 95% CI, 0.74-0.91) was lowest with intakes of at least 175 g/week. There was no further apparent decrease in HR with consumption of 350 g/week or more. Consumption of fish with higher amounts of omega-3 fatty acids was strongly associated with a lower risk of CVD (HR, 0.94; 95% CI, 0.92-0.97 per 5-g increment of intake). A lower risk was found among patients with vascular disease. This benefit was not seen in general populations without CVD (for major CVD, I2 = 82.6 [P = 0.02]; for death, I2 = 90.8 [P = 0.001]).
This well-designed meta-analysis of pooled data from four studies revealed a strong correlation between eating fish with more omega-3 fatty acids and lower risk of CVD among patients with vascular disease. This observation is in accordance with other studies. The 1989 DART trial reported a 29% reduction in all-cause mortality over a two-year follow-up in male myocardial infarction survivors when advised to increase their intake of oily fish to 200 g/week to 400 g/week.5
Hu et al conducted a meta-analysis of data from 13 trials and found a positive correlation between consumption of marine omega-3 fatty acid supplementation and lowered risk for myocardial infarction, coronary heart disease (CHD) death, total CHD, CVD death, and total CVD.6 Mohan et al recommend eating at least two servings of fish rich in omega-3 fatty acids per week in patients with preexisting CVD. This is consistent with the recommendations made by the American Heart Association.7
The authors used appropriate statistical measures. The problem statement is well-articulated and based on a sound hypothesis. The research topic is relevant to the complementary and alternate medicine approach while dealing with cardiovascular morbidity and mortality. The conceptual framework is explicit and well-justified, and the constructs investigated are clearly identified and presented. The authors have conducted a thorough and well-researched review of the literature. However, the gaps in the available literature could have been better highlighted.
The study conforms to external validity by considering participants, settings, and conditions. The internal validity is maintained by addressing potential confounding variables and biases. Given the information provided by the analysis, clinicians should feel confident prescribing 175 g (approximately two servings) of fish rich in omega-3 fatty acids twice a week for patients with prior CVD.
- Filion KB, El Khoury F, Bielinski M, et al. Omega-3 fatty acids in high-risk cardiovascular patients: A meta-analysis of randomized controlled trials. BMC Cardiovasc Disord 2010;10:24.
- Mozaffarian D, Wu JH. Omega-3 fatty acids and cardiovascular disease: Effects on risk factors, molecular pathways, and clinical events. J Am Coll Cardiol 2011;58:2047-2067.
- Rizos EC, Ntzani EE, Bika E, et al. Association between omega-3 fatty acid supplementation and risk of major cardiovascular disease events: A systematic review and meta-analysis. JAMA 2012;308:1024-1033.
- Fialkow J. Omega-3 fatty acid formulations in cardiovascular disease: Dietary supplements are not substitutes for prescription products. Am J Cardiovasc Drugs 2016;16:229-239.
- Burr ML, Fehily AM, Gilbert JF, et al. Effects of changes in fat, fish, and fibre intakes on death and myocardial reinfarction: Diet and reinfarction trial (DART). Lancet 1989;2:757-761.
- Hu Y, Hu FB, Manson JE. Marine omega-3 supplementation and cardiovascular disease: An updated meta-analysis of 13 randomized controlled trials involving 127,477 participants. J Am Heart Assoc 2019;8:e013543.
- Jain AP, Aggarwal KK, Zhang P-Y. Omega-3 fatty acids and cardiovascular disease. Eur Rev Med Pharmacol Sci 2015;19:441-445.
Is there enough scientific evidence to suggest associations between fish consumption and risk of cardiovascular disease (or of mortality) among people who consume fish vs. those who do not?
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